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Science and Islam

How Did the Prophet ﷺ Know? Embryology, Genetics, and the Hadith of the Nutfah

32 min read 7138 words

The Prophet ﷺ described, fourteen centuries ago, biological realities that Western science only confirmed in the twentieth century — among them the precise mechanism of fetal sex determination, the six-week threshold of gonadal differentiation, and the indestructibility of the primitive streak (عجب الذنب), the very structure that modern embryology identifies as the organizer and builder of the human body.

This research paper was compiled by Dr. Ahmad al-Shami (22/4/2023) and draws exclusively on peer-reviewed studies, authoritative embryology textbooks, and primary scientific literature.


Table of Contents

Part One — Fetal Sex Determination (جنس الجنين)

Definition of Sex Determination

Sex determination is a cascading molecular process, not a single event — it begins at fertilization but its visible effects do not manifest until the sixth week of embryonic life.

Peter Goodfellow & Robin Lovell-Badge — Advances in Genome Biology, Vol. 4

Peter Goodfellow and Robin Lovell-Badge, among the most celebrated geneticists of the twentieth century — famous for discovering the role of the SRY gene in sex determination — define it as follows:

“Sex determination is the process of choosing either the male or the female sexual differentiation pathway.”

ADVANCES IN GENOME BIOLOGY: Volume 4. GENETICS OF SEX DETERMINATION, by RAM S. VERMA, The Long Island College Hospital–SUNY Health Science Center Brooklyn, New York, VIII. DEVELOPMENTAL PROCESSES: SEX DETERMINATION AND DIFFERENTIATION, pg13.

Benjamin Willier — Sex and Internal Secretions (1939)

The eminent embryologist Benjamin Willier offers the following definition:

“Zygotic determination of sex is meant the primary determining constitution established in the fertilized egg by the union of the gametes…; that is the nuclear determiners or genes which decide whether male or female sex characters shall develop…. By sexual differentiation is meant the origin or expression of sex differences during ontogeny.”

Willier, B.H. The embryonic development of sex. In: Sex and Internal Secretions (Allen, E., Ed.), 2nd ed., Baillière, Tindall and Cox, London, 1939, pp.13–14.

The following diagram from Developmental Biology (6th edition) illustrates the complete gonadal differentiation pathway — from the undifferentiated gonadal ridge through to either testis or ovary, governed by a cascade of genes including SRY, SOX9, DAX1, WNT4, and SF1:

sex determination gonadal pathway diagram
sex determination gonadal pathway diagram

The second diagram shows the full genetic pathway in both the XY (7th week) and XX (7th week) gonadal ridge, with all regulatory genes mapped:

sex determination genetic pathway xx xy
sex determination genetic pathway xx xy

Source: Developmental Biology, 6th edition — Chromosomal Sex Determination in Mammals


Factors Affecting Sex Determination

The process of sex determination in mammals operates through three distinct, sequential stages:

Quinn A. & Koopman P. — European PMC (2012)

“The process of sex determination in mammals normally unfolds in three distinct stages: (1) establishment of chromosomal sex at fertilization (XX or XY); (2) commitment to the appropriate pathway of gonadal differentiation with respect to chromosomal sex, through the action (or absence) of the Y chromosome gene SRY; and (3) correct development of secondary sexual characteristics, including internal and external genitalia, in accordance with gonadal sex. At any of these three steps, the process of sex determination can go awry, leading to disorders of sexual development.”

Koopman P., abstract. The molecular genetics of sex determination and sex reversal in mammals. By Quinn A. europepmc.org

The three factors are:

  1. Chromosomal sex

  2. Gonadal sex

  3. Development of external and internal genitalia


The Sex Reversal Phenomenon

XX males and XY females are a documented biological reality in mammals including humans — a finding that demonstrates sex determination is a genetic process requiring active molecular instruction, not a passive consequence of chromosome possession.

RAM S. VERMA — Advances in Genome Biology, Vol. 4 (Introduction)

“The fortuitous findings of XX males and XY females, which are generally termed sex reversal phenomenon, are quite bewildering traits that have caused much amazement concerning the pairing mechanism(s) of the pseudoautosomal regions of human X and Y chromosomes at meiosis.”

ADVANCES IN GENOME BIOLOGY: Volume 4. GENETICS OF SEX DETERMINATION, by RAM S. VERMA, The Long Island College Hospital–SUNY Health Science Center Brooklyn, New York, intro, pg XIII

RAM S. VERMA — Advances in Genome Biology, Vol. 4 (Section VII)

“Many examples of XX males and XY females are known in different mammalian species, including the human one.”

ADVANCES IN GENOME BIOLOGY, Vol. 4, VII. SEX REVERSAL, pg10–11

Regarding the Dosage-Sensitive Sex Reversal Gene (DSS):

RAM S. VERMA — Advances in Genome Biology, Vol. 4 (Section XI)

“One of these causes failure of testis development when present in double dose on the same X chromosome. It has been named DSS (dosage sensitive sex reversal gene).”

ADVANCES IN GENOME BIOLOGY, Vol. 4, XI. TESTIS-DETERMINING GENES, pg18


The Role of SRY

SRY expression commences between days 41 and 44 post-fertilization in humans — a fact corroborated by no fewer than five independent research teams across two decades.

Anthony W. Norman & Helen L. Henry — Hormones, pg267

“The SRY gene product, SRY, is detected in the bipotential gonad of XY individuals at about 42 days.”

Hormones, by Anthony W. Norman and Helen L. Henry, pg267. Google Books

Rodolfo Rey, Nathalie Josso & Chrystèle Racine — Sexual Differentiation (2020)

“The chromosomal sex of the embryo is established at fertilization. However, 6 weeks elapse in humans before the first signs of sex differentiation are noticed. Sex differentiation involves a series of events whereby the sexually indifferent gonads and genitalia progressively acquire male or female characteristics. Believed initially to be governed entirely by the presence or absence of the SRY gene on the Y chromosome…. The presence or absence of primordial germ cells, of extragonadal origin, also has a sexually dimorphic relevance. Subsequently, internal and external genitalia will follow the male pathway in the presence of androgens and anti-Müllerian hormone (AMH), or the female pathway in their absence.”

Sexual Differentiation, by Rodolfo Rey, MD, PhD, Nathalie Josso, MD, PhD, and Chrystèle Racine, PhD., abstract. ncbi.nlm.nih.gov/books/NBK279001/

Rodolfo Rey et al. — Sexual Differentiation (2020), SRY Section

“Owing to its Y-chromosome localization, SRY can only be expressed in the XY gonadal ridge, thus playing a paramount role in tilting the balance between testicular and ovarian promoting genes towards the male pathway. A tight regulation of SRY expression is essential for fetal gonadogenesis: both timing and level of expression are determinant, as revealed by experiments in mouse showing that SRY levels must reach a certain threshold at a certain stage of fetal development to induce testis differentiation. SRY expression commences between days 41 and 44 post-fertilization in humans.”

Sexual Differentiation — Sex-Determining Region on the Y Chromosome (SRY). ncbi.nlm.nih.gov/books/NBK279001/

This information is corroborated by a dedicated study from the University of Manchester and Newcastle University by Dr. Neil Hanley, Dr. Donna Hagan, and ten additional researchers, entitled “SRY, SOX9, and DAX1 expression patterns during human sex determination and gonadal development, 2000”:

Hanley NA, Hagan DM, et al. — Mechanisms of Development (2000)

“SRY expression commences in the gonadal ridge of 46,XY embryos between 41 and 44 d.p.o./CS17–18. Peak SRY expression is detected at 44 d.p.o./CS18, when sex cords are first visible, thereby defining testicular determination.”

Hanley NA, Hagan DM, Clement-Jones M, Ball SG, Strachan T, Salas-Cortes L, McElreavey K, Lindsay S, Robson S, Bullen P, Ostrer H, Wilson DI. SRY, SOX9, and DAX1 expression patterns during human sex determination and gonadal development. Mech. Dev. 2000;91:403–407. sciencedirect.com

The following diagram from that study summarizes the role of SRY and shows how the state of testicular and ovarian formation changes before and after the end of the sixth week:

sry sox9 dax1 expression gonadal ridge week7
sry sox9 dax1 expression gonadal ridge week7

A 1990 study published in Letters to Nature by 13 researchers stated:

Letters to Nature — 13 researchers (1990)

“In conclusion, a de novo mutation in the gene SRY is associated with sex reversal in an XY female. This provides compelling evidence that SRY is required for testis formation and male sex determination.”

From a study entitled “A human XY female with a frameshift mutation in the candidate testis-determining gene SRY” (1990):

Ralf J. Jager, Maria Anvrett, Kerstin Hall & Gerd Scherer — Nature (1990), pg452

“The primary decision about male or female sexual development of the human embryo depends on the presence of the Y chromosome, more specifically on a gene on the Y chromosome encoding a testis-determining factor, TDF. ….In this region there is a candidate gene for TDF, termed SRY, which is conserved and specific to the Y chromosome in all mammals tested….We have now identified a mutation in SRY in one out of 12 sex-inversed XY females with gonadal dysgenesis who do not lack large segments of the short arm of the Y chromosome.”

From a study by Robin Lovell-Badge and Elizabeth Robertson on “XY female mice resulting from a heritable mutation in the primary testis-determining gene, Tdf”:

Robin Lovell-Badge & Elizabeth Robertson

“In mammals, it is known that the activity of a gene on the Y chromosome is responsible for determining the primary sex of the developing embryo (Jacobs and Strong, 1959; Ford et al. 1959; Welshons and Russell, 1959).”

2u.pw/HMkunD

Rodolfo Rey, Nathalie Josso & Chrystèle Racine — Sexual Differentiation (2020)

“In the absence of the Y chromosome, the bipotential gonad follows the ‘default’ ovarian pathway, which has been postulated to involve a set of ovary-determining genes (Eicher and Washburn, 1986)…. There are also many cases of human XY females. Some of these are due to chromosomal abnormalities; for example, where the region carrying TDF has been lost due to abnormal X:Y interchange at meiosis. Others may represent mutations within TDF.”

Scott F. Gilbert — Developmental Biology, 6th edition — Chromosomal Sex Determination in Mammals

“SRY is found in normal XY males and in the rare XX males, and it is absent from normal XX females and from many XY females.”

O.P. Tandon & Y. Tripathi — Best & Taylor’s Physiological Basis of Medical Practice, pg937

“SRY encodes a high-motility group (HMG) box type protein that controls the expression of other genes including the steroidogenic factor 1 (SF1), Wilms’ tumor-related gene (WT1), HMG-box 3 (SOX3) and HMG-box 9 (SOX9) required for testicular development.”


Gonadal Differentiation Does Not Begin Until After the Sixth Week

Male and female embryos are morphologically indistinguishable until Day 42 — confirmed by every major obstetrics and embryology textbook.

Albert Singer, Howard Jones & Mahmood Shafi — The Cervix (1976), pg7

“Until approximately 42 days, Carnegie stage 17, this ridge forms the indifferent gonad, and male and female embryos are morphologically indistinguishable.”

David M. Luesley & Mark Kilby — Obstetrics & Gynaecology: An Evidence-based Text for MRCOG, Third Edition (2016)

“The gonad remains undifferentiated until around 42 days.”

Sadhana Gupta — A Comprehensive Textbook of Obstetrics and Gynecology (2011), pg72

“Male and female embryos are morphologically indistinguishable till 42 days.”

Textbook for MRCOG-1: Basic Sciences in Obstetrics & Gynaecology, pg274

“The appearance of the primitive gonad is similar in both sexes until 42 days after fertilization.”

Rodolfo Rey, Nathalie Josso & Chrystèle Racine — Sexual Differentiation (2020) — The Bipotential Gonad

“No sexual difference can be observed in the gonads until the 6th week of embryonic life in humans. Undifferentiated gonads of XX or XY individuals are apparently identical and can form either ovaries or testes. This period is therefore called the indifferent or bipotential stage of gonadal development.”

ncbi.nlm.nih.gov/books/NBK279001/

Rodolfo Rey et al. — Sexual Differentiation (2020) — FGF9 and PGD2 Section

“In the 6th week of embryonic life, the gonadal ridge is sexually undifferentiated, and various factors are expressed at the same levels in the XX and the XY gonads. During the 7th week, in the XY gonad, SRY expression is triggered, and the male pathway prevails…. In the XX gonad, the female pathway prevails.”

ncbi.nlm.nih.gov/books/NBK279001/

Eske Bendsen, Anne Grete Byskov, et al. (2003)

“Sexual differentiation begins at ~6 weeks post conception (p.c.) (Witschi, 1963; Wartenberg, 1982; Lovell-Badge and Robertson, 1990), governed by the sex-determining region on the Y-chromosome (Lovell-Badge and Robertson, 1990; Koopman et al., 1990).”

H. Wartenberg — Anat. Embryol. (1982)

“In the female gonad the indifferent period terminates between day 40 and 42 of ovulation age (20 to 23 mm CR length). Between day 40 and 50 the blastemal content of the indifferent gonad is remodelled and an ovarian cortex differentiates.”

link.springer.com

The same study provides the following table of prespermatogonia counts beginning from Week 6:

| Fetal age p.c. (weeks + days) | Fetal ID | No. of prespermatogonia | No. of Sertoli cells |

|---|---|---|---|

| 6 + 0 | 1 | 2,890 | — |

| 7 + 0 | 2 | 13,459 | 133,712 |

| 7 + 4 | 3 | 15,510 | 178,372 |

| 8 + 0 | 4 | 25,708 | 395,771 |

| 8 + 1 | 5 | 36,340 | 338,122 |

| 8 + 2 | 6 | 25,593 | 287,313 |

| 8 + 2 | 7 | 19,677 | — |

| 8 + 2 | 8 | 26,338 | — |

| 9 + 0 | 9 | 17,498 | — |

| 9 + 1 | 10 | 40,585 | 431,645 |

Romina P. Grinspon & Rodolfo A. Rey — Molecular Characterization of XX Maleness (2019)

“Irrespective of their sex-chromosome constitution, all mammalian embryos are anatomically, histologically and functionally undifferentiated from a sexual standpoint during the first stages of development, approximately six weeks in humans and 10 days in mice.”


First Production of Estradiol and Testosterone — Seventh Week

Functional hormonal differentiation begins at the seventh week — even before histological differentiation is visible in the XX gonad.

Rodolfo Rey et al. — Sexual Differentiation (2020) — Ovarian Morphogenesis

“In the XX fetus, the gonad remains histologically undifferentiated after the 7th week from a histological standpoint, but a functional differentiation is already detectable: XX gonads become capable of estradiol production at the same time as XY gonads begin to synthesize testosterone.”

ncbi.nlm.nih.gov/books/NBK279001/

Institute of Medicine — Exploring the Biological Contributions to Human Health: Does Sex Matter? (2001), pg57

“Leydig cells are first found at about 60 days of gestation. Leydig cells secrete testosterone, the regulator of male differentiation.”

Rafał P. Piprek — Molecular Mechanisms of Cell Differentiation in Gonad Development (2016), pg354

“In Leydig cells, SF1 activates the expression of steroidogenic enzyme systems from the 8th week of gestation, which results in androgenization of the external genitalia.”

Ora Hirsch Pescovitz & Erica A. Eugster — Pediatric Endocrinology: Mechanisms, Manifestations, and Management (2004), pg257

“Secretion of testosterone by the interstitial Leydig cells begins at approximately 9 weeks of gestation.”

R.A. Word, F.W. George, J.D. Wilson & B.R. Carr — PubMed (Abstract)

“Androgen secretion by the fetal testis is essential for male phenotypic differentiation. In the human fetus testosterone formation is initiated soon after the differentiation of the testis (approximately 8 weeks of gestation).”

pubmed.ncbi.nlm.nih.gov/2732296/

See also: Textbook of Medical Physiology, 3rd Edition, by Indu Khurana, Arushi Khurana, Narayan Gurukripa Kowlgi, pg729. Google Books


The Role of WNT4

Qiaomu Hu et al. — Scientific Reports / Nature (2014)

“The absence of WNT4 in female embryos (XX) leads to masculinization.”

Cloning and characterization of wnt4a gene and evidence for positive selection in half-smooth tongue sole (Cynoglossus semilaevis). nature.com/articles/srep07167

Individuals who have a duplication of the chromosome containing the wnt4 gene exhibit sex reversal.


The Role of SOX9

Rodolfo Rey et al. — Sexual Differentiation (2020) — SRY Section

“Gain-of-function of SOX9 in XX individuals leads to sex reversal.”

ncbi.nlm.nih.gov/books/NBK279001/

Romina P. Grinspon & Rodolfo A. Rey — Molecular Characterization of XX Maleness (2019) — SOX9 Section

“On the other hand, increased expression of SOX9 in XX gonads induces testicular differentiation resulting in foetal virilisation even in the absence of SRY…. Male differentiation can occur in XX individuals in the presence or the absence of SRY.”

Scott F. Gilbert — Developmental Biology, 6th edition

“XX humans who have an extra copy of SOX9 develop as males, even though they have no SRY gene (Huang et al. 1999).”

Khadilkar Vaman — IAP Textbook on Pediatric Endocrinology, pg264

“6–7 WEEKS: SRY expression and SOX9 expression transforming progenitor cells to pre-sertoli cells (testes determination). Also role of (WT1, SF1, DMRT1/2, DHH, ATRX, SOX8, ARX). 7 weeks: Sertoli cell differentiation (Fgf9 & Fgfr2) leads to primary sex cords, phenotypic sex.”

Aron T. Cory, Alexandre Boyer, Nicolas Pilon, Jacques G. Lussier & David W. Silversides

“In mammals, the pre-Sertoli cell of the male genital ridge is the first cell type to display sex-specific differentiation and differential gene expression.”

Presumptive pre-Sertoli cells express genes involved in cell proliferation and cell signalling during a critical window in early testis differentiation.


Anti-Müllerian Hormone (AMH)

Freddie C. Hamdy & Ian Eardley — Oxford Textbook of Urological Surgery, pg1015

“Anti-Müllerian hormone (AMH) is a glycoprotein hormone secreted by pre-Sertoli cells of the testis from around the seventh week onwards.”

Anthony Zietman & Murray Brookes — Clinical Embryology: A Color Atlas and Text, pg216

“Sertoli cells….from the 7th week onwards, these secrete anti-Müllerian hormone.”


Insulin-like Hormone-3 (INSL3)

Nathalie Josso, Rodolfo A. Rey & Andrew Pask — Fetal Testicular Hormones, pg8

“This gene may be involved in the development of urogenital tract and female fertility.”

National Library of Medicine, National Center for Biotechnology Information. ncbi.nlm.nih.gov/gene/3640

The following graph shows INSL3 mRNA expression levels measured by microarray analysis of gonadal tissue from individual male (blue triangles) and female (red circles) human fetuses across fetal age in days post-conception:

insl3 mrna expression male female fetuses
insl3 mrna expression male female fetuses

Oxford Textbook of Urological Surgery — Key Testicular Supporting Cells, Week 8

“By week 8 of gestation, two key supporting cells of the testis can be identified: Sertoli cells, which line the seminiferous tubules, and Leydig cells, which populate the interstitium. Two key gene products are secreted from these cells that direct the future function of the gonad and the final determination of the internal genital ductal system. The first hormone, produced by Sertoli cells, is mullerian inhibitory substance….. Sertoli cells also express desert hedgehog gene, a molecule that plays an important role in spermatogenesis. Secretion of testosterone by the interstitial Leydig cells begins at approximately 9 weeks of gestation.”


Then We Created of the Clot Another Thing

Richa Saxena — Textbook for MRCOG-1: Basic Sciences in Obstetrics and Gynaecology, pg238

“When the embryo becomes 7 or 8 weeks old, it is known as a ‘foetus’.”

Overexpression of DMRT1 in XX mice inhibits WNT4 and FOXL2 expression and results in partial testicular differentiation and male genital development. (Sexual Differentiation, by Rodolfo Rey, Nathalie Josso, Chrystèle Racine, abstract.)

The following image shows the embryo at Carnegie Stage 10 (approximately the 7–8 week mudgha/foetus transition), sourced from the Endowment for Human Development:

mudgha embryo carnegie stage10
mudgha embryo carnegie stage10

Reference: ehd.org/developmental-stages/stage10.php

The following two panels show human embryo developmental stages (A, B, C, D) from the clinical embryology atlas:

embryo developmental stages abcd panels
embryo developmental stages abcd panels

The Hamburger-Hamilton stage comparison below shows corresponding developmental stages across 4S–12S in the chick embryo model, used in comparative embryological research:

hamburger hamilton chick embryo stages
hamburger hamilton chick embryo stages

Reference: researchgate.net — Hamburger-Hamilton stage 10 chick embryo showing development of somites


Part Two — The Bones (العظام)

(A complete detailed separate study is available)

The Clavicle — First Bone to Ossify

The clavicle is the first bone in the human skeleton to begin ossification — appearing at approximately Day 39, at the end of the sixth week of intra-uterine life.

Robert Carachi & Sameh Helmi Edward Doss — Clinical Embryology: An Atlas of Congenital Malformations, pg29

“Weeks 6–7: The clavicle (first bone to ossify) begins to ossify.”

Louise Scheuer, Sue Black & Craig Cunningham — Osteology, pg23

“The clavicle is probably the first bone in the human skeleton to show evidence of bone formation, which can be detected in the differentiating mesenchyme from approximately day 39 in the sixth week of intra-uterine life.”

books.google.com.sa — Osteology

The following diagram from Clinical Embryology An Atlas of Congenital Malformations shows the neural tube development and related bone formation anatomy:

neural tube bone formation diagram
neural tube bone formation diagram


Part Three — The Eye (العين)

The duration of eye formation extends from approximately the first week to the seventh week.

The Eight Parts of the Eye

Eye Anatomy: Parts of the Eye and How We See; By Kierstan Boyd, David Turbert; Reviewed By Ninel Z Gregori, MD — aao.org

The diagram below identifies the eight anatomical components of the human eye — all of which begin development by the seventh week:

eye anatomy eight parts diagram
eye anatomy eight parts diagram

Kathleen Scogna, medically reviewed by Judith Venuti Ph.D. — BabyCenter (2022)

“At about 7 weeks, the main parts of the eye that enable sight – the cornea, iris, pupil, lens, and retina – start developing.”

How your baby’s eyes and vision develop in the womb. babycenter.com


Stages of Eye Formation — Week by Week

The three major phases of eye development are:

  1. Embryogenesis — formation of primary organ rudiments, ending at the end of Week 3

  2. Organogenesis — development of primary organ rudiments, extending to the end of Week 8

  3. Differentiation — division of each primitive organ into a fully or partially functional organ

Y.R. Barishak — Embryology of the Eye and Its Adnexae (1992)

“The first period called embryogenesis is characterized by the establishment of the primary organ rudiments and ends at the end of the 3rd week with the appearance of the optic sulci on both sides of the midline at the expanded cranial end of the still open neural folds. The second period called organogenesis includes the development of the primary organ rudiments and extends till the end of the 8th week. The third period involves the differentiation of each of the primitive organs into a fully or partially active organ and is called differentiation.”

pubmed.ncbi.nlm.nih.gov/1628748/

The cross-sectional diagram below shows the eye at Week 5, with the optic stalk, lens vesicle, vitreous body, retinal and choroid fissure all visible:

eye development week5 cross section
eye development week5 cross section

The image below shows eyelid formation in a human embryo at eight weeks gestation:

eyelid formation week8 embryo
eyelid formation week8 embryo

Linda Conlin BS, ABOC, NCLEC — 20/20 Magazine (2012)

“The human eye begins to develop during the 17th day of gestation.”

Embryonic Eye Development. 2020mag.com

Parker E. Ludwig, Michael J. Lopez & Craig N. Czyz — Embryology, Eye Malformations (2022)

“Eye development occurs in the human embryo from approximately the third week through the tenth week of gestation.”

ncbi.nlm.nih.gov/books/NBK482496/

Edward DP & Kaufman LM — Anatomy, Development, and Physiology of the Visual System (2003)

“The appearance of optic grooves (neuroectoderm origin) from the developing forebrain marks the first sign of eye development at week three of gestation.”

ncbi.nlm.nih.gov

Week 2 — Formation of the Eyeball Begins:

Dr. Yogesh Sontakke MBBS MD (Anatomy) — eOphtha (2021)

“The eyeball development begins early in the 4th week of intrauterine life with formation of optic vesicle (a diverticulum) from diencephalon.”

eophtha.com

E.R. Tamm — Encyclopedia of the Eye (2010)

“Embryologic eye development begins at 4–5 weeks of gestation (27–36 days) during lens vesicle formation.”

sciencedirect.com

Linda Conlin — Embryonic Eye Development (2012)

“To all that activity, add the formation of the orbits and extraocular muscles at four weeks gestation.”

Neuroanatomy Lab Resource Appendices — Temple University LKSOM

“Early in the 4th week optic vesicles extend from the 3rd ventricle and wall of the forebrain (diencephalon). As the vesicle reaches the surface ectoderm it flattens (a) and progressively invaginates (b) to form the optic cup.”

lksom.temple.edu

The following information panel records the key events at Day 25:

day25 optic vesicles neural crest
day25 optic vesicles neural crest

Week 3 — Trilaminar Disc, Optic Sulcus, Retinal Pigmentation:

Aaron Warning MD & Vatinee Y. Bunya MD MSCE — EyeWiki (AAO)

“By the third week of development, the three germ layers are arranged in a flat disc-like structure called the trilaminar disc, which marks a key milestone towards the formation of the developing embryo.”

eyewiki.aao.org

Clinical Anatomy and Physiology of the Visual System, 3rd ed. (2012) — Elsevier, pg130

“Pigmentation of the retinal epithelium occurs at approximately week 3 or 4; this is the earliest pigmentation evident in the embryo.”

The Day 33 panel below records the closure of the embryonic fissure — a key developmental milestone:

day33 embryonic fissure closes
day33 embryonic fissure closes

Week 4 — Eyelids Begin, Lens Placode (Day 27), Choriocapillaris:

Travis R. Bales, Michael J. Lopez & Jeremy Clark — Embryology, Eye (2022)

“At approximately week six of gestation the eyelids begin to form.”

ncbi.nlm.nih.gov/books/NBK538480/

K. SELLHEYER — Development of the Choroid and Related Structures (1990), pg255

“The choriocapillaris starts to differentiate simultaneously with the development of the retinal pigment epithelium during the fourth and fifth week.”

nature.com/articles/eye199037.pdf

Week 5 — Lacrimal Glands, Lens (Day 35), Sclera, Hyaloid Artery, Neuroblastic Layers:

Jacob Cook — The Embryology of the Eye (Eye News)

“The lens begins development from an out-pouching of the surface ectoderm at approximately day 35.”

eyenews.uk.com

Linda Conlin — Embryonic Eye Development (2012)

“At seven weeks, the sclera develops from embryonic tissue.”

Clinical Anatomy and Physiology of the Visual System, 3rd ed. (2012) — pg128

“A branch of the internal carotid artery enters the optic cup through the fetal fissure to become the hyaloid artery during week 5.”

Clinical Anatomy and Physiology of the Visual System, 3rd ed. (2012) — pg130

“At approximately week 7, cell migration occurs, forming the inner and outer neuroblastic layers, between which lies the transient fiber layer of Chievitz.”

Week 6 — Optic Stalk to Brain (Day 36), Lacrimal Glands, Ganglion Cell Axons, Optic Nerve:

Linda Conlin — Embryonic Eye Development (2012)

“The optic stalk, the precursor to the optic nerve, forms a critical connection to the forebrain at 36 days.”

Clinical Anatomy and Physiology of the Visual System, 3rd ed. (2012) — pg126

“Formation of optic nerve occurs between sixth and eighth weeks.”

Kathleen Scogna — BabyCenter (2022)

“8 weeks: Tear ducts start to develop.”

babycenter.com

Clinical Anatomy and Physiology of the Visual System, 3rd ed. (2012) — pg135

“By week 8, a second wave of mesenchyme proliferates, migrates between the developing epithelium and endothelium, and gives rise to the fibroblasts, collagen, and ground substance of the stroma.”

K. SELLHEYER — Development of the Choroid and Related Structures (1990), pg256

“Although rarely seen, pericytes can be detected as early as the sixth week.”

nature.com/articles/eye199037.pdf

The comprehensive eyelid development timeline table below, compiled from 11 sources, maps all eyelid structural events from Week 6 through Week 20:

eyelid development timeline table
eyelid development timeline table

Reference: ncbi.nlm.nih.gov/pmc/articles/PMC5102278/

Week 7 — Completion of Iris, Anterior Tunica Vasculosa Lentis, Basal Lamina:

Linda Conlin — Embryonic Eye Development (2012)

“Between 30 and 35 days, you can see the start of the iris. In two more weeks, it is fully developed.”

Clinical Anatomy and Physiology of the Visual System, 3rd ed. (2012) — pg129

“The annular vessel sends loops forward onto the anterior surface of the lens to form the anterior vascular tunic of the lens (anterior tunica vasculosa lentis) during the seventh week.”

Clinical Anatomy and Physiology of the Visual System, 3rd ed. (2012) — pg134

“The first component of the anchoring system is the basal lamina, which is evident by week 9, and hemidesmosomes are present by week 13.”

Week 10 — Bowman’s Layer, Iris Epithelium, Pupillary Membrane:

Clinical Anatomy and Physiology of the Visual System, 3rd ed. (2012) — pg135

“At 3 months all layers of the cornea are present, except Bowman’s layer, which appears during the fourth month.”

Clinical Anatomy and Physiology of the Visual System, 3rd ed. (2012) — pg137

“By the end of the third month, the lip of the optic cup begins to elongate and grows between the lens and the developing cornea. The outer layer of the optic cup becomes the anterior iris epithelium and the inner layer forms the posterior iris epithelium.”

Clinical Anatomy and Physiology of the Visual System, 3rd ed. (2012) — pg137

“During the third month, the pupillary membrane forms between the lens epithelium and the corneal endothelium to replace the vascular tunic.”

Week 11 — Fusion of Eyelid Folds:

3months eyelid folds fuse
3months eyelid folds fuse

Week 14 — Zonular Fibers, Lamina Cribrosa, Aqueous Humor, Trabecular Meshwork:

Clinical Anatomy and Physiology of the Visual System, 3rd ed. (2012) — pg130

“During the fourth month, vessels of hyaloid system atrophy progressively. Zonular fibers (tertiary vitreous) begin to stretch from the growing ciliary region toward the lens capsule.”

Clinical Anatomy and Physiology of the Visual System, 3rd ed. (2012) — pg135

“During the fourth month connective tissue fibers cross the posterior scleral foramen, running through the optic nerve fibers and producing the first connective tissue strands of the lamina cribrosa.”

Clinical Anatomy and Physiology of the Visual System, 3rd ed. (2012) — pg135

“Aqueous humor production begins at 4 to 6 months of gestation.”

Clinical Anatomy and Physiology of the Visual System, 3rd ed. (2012) — pg138

“The trabecular meshwork is visible as a triangular mass of mesenchymal cells during the fourth month.”

Week 18 — Ciliary Muscle, Myelination:

Clinical Anatomy and Physiology of the Visual System, 3rd ed. (2012) — pg135

“The ciliary muscle begins to develop from neural crest during the fifth month.”

Clinical Anatomy and Physiology of the Visual System, 3rd ed. (2012) — pg138

“Myelination of the axon begins during the fifth month of gestation once the fiber reaches the lateral geniculate nucleus.”

Week 20 — Eyelid Separation, Photoreceptor Cells:

Linda Conlin — Embryonic Eye Development (2012)

“During the fifth month, a two-month process begins — the separation of the eyelids.”

Clinical Anatomy and Physiology of the Visual System, 3rd ed. (2012) — pg130

“The photoreceptor cells are the last cells of neural retina to differentiate; this occurs during the fifth month.”


Part Four — The Role of the Ovum in Sex Determination

The Ovum Selects the Sperm

The egg is not a passive recipient — it actively selects sperm based on genetic content — a finding that challenges the foundational assumption of Mendelian random gamete union.

Carrie Arnold — Quanta Magazine (2017)

“The oldest law of genetics says that gametes combine randomly, but experiments hint that sometimes eggs select sperm…”

Choosy Eggs May Pick Sperm for Their Genes, Defying Mendel’s Law. quantamagazine.org

This is based on research by Dr. Joseph H. Nadeau of Oxford University, published under the title “Do Gametes Woo? Evidence for Their Non-random Union at Fertilization”:

Carrie Arnold — Quanta Magazine (2017) — quoting Nadeau’s hypothesis

“His hypothesis — that the egg could woo sperm with specific genes and vice versa — is part of a growing realization in biology that the egg is not the submissive, docile cell that scientists long thought it was. Instead, researchers now see the egg as an equal and active player in reproduction.”

Joseph H. Nadeau — Genetics Journal / Oxford Academic

“These unusual results suggest that fertilization is genetically biased toward particular gametes based on their genetic content.”

Do Gametes Woo? Evidence for Their Nonrandom Union at Fertilization. academic.oup.com

Polina V. Lishko et al. — PubMed Central (2011)

“The female reproductive tract has the capacity to select and orient sperm, making it an active recipient of male gametes.”

The Control of Male Fertility by Spermatozoon Ion Channels. ncbi.nlm.nih.gov/pmc/articles/PMC3914660/


Vaginal pH and Fetal Sex

Normal vaginal pH range: 3.8–4.5

A study entitled “Effect of Vaginal pH in Preconceptional Fetal Sex Determination” by Dr. Mohammed Gaber (Professor of Dermatology and Venereology, Menoufia University) and Dr. Saeed Salah (Professor of Obstetrics and Gynecology, same faculty) concluded that fetal sex can be determined based on vaginal pH. Study parameters:

  • 20 patients from Menoufia University clinics, ages 21–37 years

  • Excluded: women with conditions affecting vaginal pH (diabetes, vaginitis, cervicitis, other significant medical problems)

  • Complete obstetric, gynecological, and medication history taken

  • Study group: 20 women at ovulation time

  • Vaginal pH measured using litmus paper at first days of ovulation

  • Vaginal ultrasound used to measure ovarian follicle diameter (reaching 20mm at ovulation) along with luteinizing hormone measurement

  • Women divided into alkaline and acidic vaginal pH groups

  • After determining fetal sex by ultrasound, correlation with acidic and alkaline vaginal pH was established

The results table below shows a statistically significant association (p = 0.007) between fetal male sex and alkaline vaginal pH, and fetal female sex and acidic vaginal pH:

vaginal ph fetal sex results table
vaginal ph fetal sex results table

Reference: mmj.eg.net — Effect of Vaginal pH in Preconceptional Fetal Sex Determination


Differences Between X and Y Sperm

X-bearing spermatozoa are statistically larger, longer, and wider than Y-bearing spermatozoa.

Dr. K.H. Cui — University of Adelaide, Australia

“Statistically, the length, perimeter and area of the sperm heads, and the length of the sperm necks and tails of X-bearing spermatozoa were significantly larger and longer than those of Y-bearing spermatozoa.”

This finding was confirmed by Joep P.M. Geraedts, Professor of Genetics and Molecular Biology at Maastricht University, Netherlands, in a study entitled “X spermatozoa larger than Y in 1973”:

Joep P.M. Geraedts — Molecular Human Reproduction, Vol. 3, Issue 6 (1997), pp. 545–546

X spermatozoa larger than Y in 1973.

academic.oup.com/molehr


Part Five — ‘Ajab al-Dhanab — The Primitive Streak

The primitive streak is the most consequential structure in early human embryogenesis — it organizes the entire body plan, determines all cell fates, and is identified by modern science as the iconic structure from which every tissue and organ of the human body originates.

The following photograph is among the earliest real images of the primitive streak:

primitive streak first photograph
primitive streak first photograph

Reference: discovery.lifemapsc.com — Embryonic Development of the Primitive Streak

The diagram below illustrates how every structure of the body arises from the primitive streak, situated at the caudal end of the hypoblast disc:

primitive streak cranial caudal diagram
primitive streak cranial caudal diagram


Functions of the Primitive Streak

The primitive streak is:

  1. The builder of all body cell types — it forms every cell type of the human body

  2. The marker of human individuality — its appearance at Day 14 is recognized internationally as the beginning of individual human identity

  3. The legal threshold in the 14-day rule — many nations establish Day 14 as the limit for experimental intervention with human embryos, as it marks the appearance of the primitive streak

  4. The controller of cell fates — it determines which cell becomes which tissue and organ

  5. The builder of the germinal layers — it produces the three germ layers (endoderm, mesoderm, ectoderm) from which all cells arise

  6. The source of developmental commands — it issues the molecular instructions required for brain formation and organ differentiation

The following Embryonic Development Ontology Tree shows how every structure of the body — from bone, blood, brain, lung, kidney, heart, and liver to the nervous system, epidermis, and reproductive system — traces back through the primitive streak to the zygote:

embryonic development ontology tree
embryonic development ontology tree

Alfonso Martinez Arias & Guojun Sheng — Science (2021)

“The primitive streak also gives anterior-posterior and dorsal-ventral spatial information to cells undergoing gastrulation and forming the various body cell types…symbolize the emergence of human individuality. As such, many countries have established a legal limit of 14 days for the in vitro culture of fertilized human eggs — this is known as the ‘14-day rule.’”

The study describes it as an iconic structure.

The primitive streak and cellular principles of building an amniote body through gastrulation. science.org/doi/10.1126/science.abg1727

Kumamoto University — SciTechDaily

“After fertilization, a human embryo implants into the uterus (day 6–12) and gastrulation starts soon afterwards, with the primitive streak emerging at about day 14. Gastrulation allocates cell fates … laying down the foundation of the human body.”

scitechdaily.com

Kumamoto University — SciTechDaily (continued)

“One of the most critical periods of development…occurs at approximately two weeks after fertilization through a process called gastrulation and is associated with an embryonic structure called the primitive streak — a structure in early development that initiates bilateral symmetry and germ layer formation.”

StatPearls — Embryology and Gastrulation

“Gastrulation is defined as an early developmental process in which an embryo transforms from a one-dimensional layer of epithelial cells (blastula) and reorganizes into a multilayered and multidimensional structure called the gastrula…gastrulation derives a three tissue-layered organism composed of endoderm, mesoderm, and ectoderm…is marked by the appearance of a groove in the caudal end of the epiblast layer known as the primitive streak.”

statpearls.com/ArticleLibrary/viewarticle/22120

In 2018, researcher Kelly Servick wrote in Science magazine an article entitled “Elusive Master Organizer of Human Embryo Growth”science.org — in which she considered the primitive streak as the answer to the question posed by Brivanlou:

Kelly Servick — Science Magazine (2018) — quoting Ali Brivanlou

“‘Where does the information come from … to make a brain or discrete organs?’ Brivanlou says.”
Elusive master organizer of human embryo growth seen for the first time. 23 May 2018. science.org

Merriam-Webster — Definition of Primitive Streak

“The embryo forms a furrow called the primitive streak and folds inward on itself while cells mature into different lineages that will later give rise to all the organs and tissues of the body.”
merriam-webster.com

Takashi Mikawa et al. — Induction and Patterning of the Primitive Streak

“The primitive streak … defines the future embryonic midline and serves as a conduit of cell migration for germ layer formation…. Once the initial primitive streak is established, germ layer formation begins.”

TeachMeAnatomy — Gastrulation

“Gastrulation is a process of cellular rearrangement which involves migration, invagination and differentiation of the epiblast. It is largely controlled and orchestrated by the primitive streak. The primitive streak is a groove in the midline of the epiblast which appears during the third week. Within the primitive streak lies a primitive node at the cranial end, and within the primitive node lies the primitive pit. Cells of the epiblast layer break off and migrate toward the primitive pit. Here, they detach and penetrate through the epiblast layer to form three new germ cell layers: Endoderm — formed by epiblast cells that migrate through the primitive pit and displace the hypoblast cells. Mesoderm — formed by epiblast cells that migrate through the primitive pit and lie between the epiblast layer and the newly created endoderm. Ectoderm — formed by the epiblast cells that remain in position. These three cell layers are then responsible for forming the different tissues of the fetus.”
teachmeanatomy.info


Study of Spemann and Mangold

Study title: “Induction of Embryonic Primordia by Implantation of Organizers from a Different Species” by Hans Spemann and Hilde Mangold.

Reference: ijdb.ehu.es/article/11291841


Every Son of Adam Will Decay Except the Coccyx

The primitive streak retains its inductive capacity even after being killed by heat, crushing, or coagulation — a fact established through multiple independent experiments.

The Prophet ﷺ said: “Every son of Adam will decay except the coccyx — from it he was created, and from it he will be reconstructed.”

C.H. Waddington — embryologist, geneticist, and founder of systems biology — in his article “Experiments on Embryonic Induction” recorded:

C.H. Waddington — Experiments on Embryonic Induction (Journal of Experimental Biology)

“Bautzmann, Holtfreter, Spemann and Mangold (1932) had shown that in the Amphibia coagulated organisers are still able to exert the inductive capacities which they possess in the living state. This work followed on the earlier experiments of Marx (1931) who obtained inductions with narcotised organisers, and Spemann (1931a) who found that the inductive capacity is retained when the organiser tissue is subjected to crushing.”
Experiments on Embryonic Induction: Part II. Experiments on Coagulated Organisers in the Chick. journals.biologists.com

Waddington himself conducted two experiments by killing the organizer with heat and found it still retained its inductive capacity:

C.H. Waddington — Experiments on Embryonic Induction — Confirmed Conclusion

“The two successful experiments 32–331 and 33–17 described above are sufficient to show that in the chick the capacity to perform an induction can be present in dead material.”
Experiments on Embryonic Induction: Part II. Experiments on Coagulated Organisers in the Chick. journals.biologists.com

This proves that the cells of the coccyx (primitive streak / عجب الذنب) were not destroyed by these processes. What was destroyed in the experiments: spinal cord cells, fat cells, and muscle cells — while the primitive streak’s inductive core remained active.


Note

This research paper will continue to be updated, God willing.
Dr. Ahmad al-Shami — 22/4/2023

2026 https://www.openislam.wiki/og/how-did-the-prophet-صلى-الله-عليه-وسلم-know-embryology-genetics-and-the-hadith-of-the-nutfah.png